Although neoplasms are commonly reported in domestic hamsters, retrospective studies approaching spontaneous tumors with data regarding epidemiological findings are scarce. The present study aimed to describe the epidemiological and pathological findings of 40 cases of tumors in domestic hamsters diagnosed in a veterinary pathology laboratory in Southern Brazil from 2002 to 2019. Chinese hamster (Cricetulus griseus) was the most commonly affected species (16/40), followed by Djungarian hamster (Phodopus sungorus, 11/40) and Syrian hamster (Mesocricetus auratus, 4/40). Among the cases, 57.5% were females (23/40), while 42.5% were males (17/40). The affected hamsters’ median age was of 14-months old, with an age range of 8- to 36-months old. Twenty-four cases were assessed as anatomopathological samples (biopsies), while 16 were composed of carcasses submitted to postmortem examination, and, therefore, the neoplasm was related to the cause of death. The integumentary system was frequently affected (60%, 24/40), followed by the female reproductive tract (22.5%, 9/40), hematopoietic system (10%, 4/40), digestive tract (5%, 2/40), and endocrine system (2.5%, 1/40). The most frequent neoplasm was squamous cell carcinoma (35%, 14/40), mostly on the lip/nasal region (50%, 7/14). Other tumors included fibrosarcoma (10%, 4/40), lymphoma (10%, 4/40), mammary cystadenoma (10%, 4/40), apocrine sweat gland adenoma (7.5%, 3/40), hemangiosarcoma (5%, 2/40), leiomyosarcoma (5%, 2/40), and granulosa ovarian cell tumor (5%, 2/40). The five remaining cases occurred individually and were composed of hepatoid gland adenoma, solid thyroid carcinoma, cutaneous melanoma, ovarian teratoma, and cutaneous trichoblastoma. Neoplasms were identified as an important cause of death and major reason to perform biopsy in domestic hamsters in Southern Brazil.