A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8–19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1–24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.