BACKGROUND Primary hepatic lymphoma is a rare malignancy which misdiagnosis and mistreatment is very frequent. Differential diagnosis of the hepatic lesion, based on the noninvolvement of blood vessels, includes: fatty infiltration, cirrhosis, amyloid infiltration, primary hepatomas, and metastatic neoplasms. METHODS We describe a case of a 69-year-old man who presented with 15% weight loss and general fatigue over the previous 9 months. Physical examination revealed hepatomegaly without lymphadenopathy or splenomegaly. Magnetic resonance imaging showed a 13cm×9cm×11cm tumor on the right liver associated with normal levels of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA). After two negatives ultrasonography-guided needle liver biopsies, the third one showed diffuse infiltration of large sized lymphoid cells. Immunohistochemical findings demonstrated the B-lymphocyte lineage of the tumor. The patient received R-CHOP therapy (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) with good response. CONCLUSIONS It is important to recognize PHL because it responds favorably to chemotherapy and may have a better prognosis than hepatocellular carcinoma or metastatic disease of the liver. When imaging findings on CT scans and MRI are nonspecific, a biopsy is needed not only for a definitive diagnosis but also for identifying the immunophenotype of the PHL. This type of lesion is highly chemosensitive and early aggressive chemotherapy may result in sustained remission. CONCLUSIONS This case emphasizes the importance of effective recognition of PHL considering its good response to chemotherapy and the possibility of sustained remission if early aggressive treatment is implemented.