Hepatoid adenocarcinoma is a rare extra hepatic neoplasm that displays morphological and phenotypic features similar to those of hepatocellular carcinoma. We report a case of a 75-year-old woman, presenting with abdominal pain and complaints of weakness and lost of appetite, who was found to have a mass on her right colon. She underwent right hemicolectomy for a pT3N2M0, stage IIIC colon cancer. The tumor phenotype and immunophenotype, as documented by alpha-fetoprotein immunoreaction positivity, were consistent with adenocarcinoma of hepatoid origin. The patient received FOLFOX-4 regimen as adjuvant treatment, relapsed after six cycles, then was switched to FOLFIRI regimen plus Bevacizumab and progressed after only four cycles. She died 1 month later, eight months after the diagnosis. The lack of any clinical benefit despite an aggressive and multimodal therapeutic strategy, raises a question about what should be targeted when we face this rare disease associated with a very poor prognosis.