ABSTRACT: BACKGROUND: Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence. RESULTS: No genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence. CONCLUSION: From these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia.