CD1 molecules might contribute to anti-tumor immune response by presentation of tumor-derived lipid and glycolipid antigens to T cells and NKT cells. Polymorphisms in CD1 genes have been suggested to modify ligand binding of CD1 molecules and thereby change the antigen presenting ability of these molecules. The aim of this study was to investigate the exon 2 polymorphisms of CD1a and CD1d in several high incident cancers in Iran. For this purpose, 201 female breast cancer patients and 207 healthy women, 64 lung cancer patients and 95 healthy individuals and 109 patients with colorectal cancer and 109 healthy controls were recruited to this study. Using PCR-SSP method, no significant correlation was found in genotype and allele frequencies of CD1a between all three studied groups and their control counterparts. Moreover, a dominant frequency of CD1d 01 (A) allele was observed in the majority of studied individuals. No significant association between the CD1 polymorphisms and prognostic factors in breast, lung and colorectal cancers was detected. Our results highlight the conserved nature of CD1 genes and may point to the immuoregulatory functions of CD1 molecules in cancer that can be exerted through fine tuning of NK, T and NKT cells.