Rectal adenocarcinoma with diffuse oncocytic features is a very rare lesion, having been reported only once in the English literature. We describe a case of oncocytic adenocarcinoma of the rectum, associated with a villous adenoma, arising on a 66-year-old man. On histological examination, the adenocarcinoma was composed of neoplastic glands lined by a strongly eosinophilic, granular epithelium that deeply infiltrated the rectal wall. Some basophilic calcifications were present in the gland lumina. Superficially, a villous adenoma with high-grade dysplasia was evident; adenomatous cells showed focal eosinophilic changes, consisting of a large granular cytoplasm, an oval atypical nucleus, and a prominent nucleolus. Immunohistochemically, neoplastic glands reacted strongly with antimitochondria antibody, carcinoembryonic antigen, cytokeratin 20, p53, and CDX2. Molecular alterations observed in oncocytic changes and their significance with regards to neoplastic transformation are briefly discussed.