PURPOSE To present a case series of primary intraosseous squamous cell carcinoma arising in odontogenic cysts and review the published data to understand the pathogenesis of the lesion. MATERIALS AND METHODS The files of the Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital (Jaipur, India) were reviewed, and 3 cases of primary intraosseous squamous cell carcinoma ex odontogenic cyst diagnosed from 2006 to 2011 were identified. The diagnostic inclusion criteria were the presence of a completely intraosseous lesion; the absence of ulceration of the oral mucosa, except when caused by other factors such as tooth extraction or trauma; and the absence of a distant primary tumor. The malignant transformation of the benign cystic lining of an odontogenic cyst to squamous cell carcinoma was identified, and the diagnosis of primary intraosseous squamous cell carcinoma ex odontogenic cyst was confirmed in all cases. The relevant English data were reviewed to determine the possible etiopathologic factors associated with the lesion. RESULTS It was observed that long-standing chronic inflammation in the benign odontogenic cyst was the most probable etiopathologic factor responsible for malignant transformation of a benign cystic lining. CONCLUSIONS The signs of chronic inflammation in odontogenic cysts should be taken into consideration, and such lesions should be treated promptly. By doing so, we might reduce the rate of malignant transformation of benign odontogenic cysts.