We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and “suspicious” for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia. Besides colloid (mucinous) carcinoma (CCA), a variety of mammary lesions might yield abundant extracellular mucinous material on fine-needle aspiration biopsy (FNAB). The cytologic features of CCA are well established.1-10 The diagnosis of malignancy on aspiration biopsy is straightforward when all the characteristic criteria are present. However, aspirates with abundant extracellular mucinous material originating from other mammary lesions, especially those with increased cellularity, may pose a diagnostic challenge on FNAB.1-10 Benign lesions, such as myxoid fibroadenoma and fibrocystic change (FCC), can mimic CCA with relatively cellular, mucin-rich smears and occasional atypical cells.7,8,11 Conversely, mucocele-like lesions (MLLs) can have a deceptively benign appearance on FNAB, and yet ductal carcinoma in situ (DCIS) or invasive ductal carcinoma may be revealed by excision, further complicating the diagnostic problem.6,7,12-14 Comparative studies describing the cytologic features in MLLs, CCA, and other benign mucinous lesions that might mimic CCA are relatively few and consist of a small number of cases.1,4,6,7,9,10 We reviewed the FNAB smears and subsequent resected specimens from 43 mammary lesions containing abundant extracellular mucinous material on aspiration biopsy to determine whether accurate classification of lesions yielding copious mucinous material can be achieved on FNAB. Materials and Methods The computerized records of the Cytopathology Division at New York University Hospitals (Tisch and Bellevue Hospitals, New York, NY) for January 1992 to December 2001 Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2003;120:194-202 195 195 DOI: 10.1309/2MKQRJ3DLPMT4LJA 195 © American Society for Clinical Pathology were searched for mammary aspiration biopsy specimens that showed abundant extracellular mucinous material with or without associated epithelial cell atypia. We identified 69 cases. The patients all were women who had palpable or nonpalpable radiologic abnormalities. Follow-up information was not available for 26 women whose FNABs were done by radiology groups at outside institutions. Aspirated material was processed and evaluated at our laboratory, and the treatment of all 26 women was managed by physician practice groups that are not affiliated with our institution. Thus, they were excluded from the study. The remaining 43 women had undergone FNAB at our institution. In this group, all underwent surgical excision 2 weeks to 3 months after the initial cytologic diagnosis. FNABs of the palpable breast nodules were performed by cytopathologists using 25or 27-gauge needles. FNABs of the nonpalpable lesions were performed by cytopathologists by a stereotaxic approach using 22-gauge spinal needles in the presence of a radiologist who targeted the lesion or by radiologists using ultrasound guidance and 23or 25-gauge needles in the presence of a cytopathologist who provided an immediate diagnosis. In each case, 2 to 8 smears were prepared. The material obtained at aspiration was expressed onto glass slides, air dried, and stained with a rapid Romanowsky–type stain (Quik-Dip stain, Mercedes Medical, Sarasota, FL), the Ultrafast Papanicolaou stain (Richard-Allan, Kalamazoo, MI), or both. The smears were reviewed and evaluated for the following features: cellularity, nuclear atypia (increased nuclear/cytoplasmic ratios, irregularities of nuclear contour, clumped chromatin, prominent nucleoli), presence of single (dissociated) ductal epithelial cells and oval bare nuclei, and the quantity of extracellular mucinous material and its association with the epithelial component. Background components such as the presence of stromal fragments, macrophages, and apocrine cells also were noted. The cellularity of smears and cellular atypia were graded on a scale from 0 (none) to 3+ (marked). A 4-tiered grading system was used instead of a 3-tiered approach to emphasize the total absence of certain evaluated features such as atypia and cellularity in some cases. The slides from corresponding resections were reviewed to confirm the diagnosis and to document the source of the mucinous material.