Large B-cell non-Hodgkin lymphoma involving the prostate accounts for 0.09% and 0.1% of non-Hodgkin lymphoma. We report a case of prostatic large B-cell non-Hodgkin lymphoma in a 77-year-old male with symptoms of urinary retention most probably due to benign prostate hyperplasia. He underwent multiple needle core biopsies through transrectal ultrasound of the prostate. Histopathological examination of the core biopsies revealed diffuse infiltration by atypical lymphoid cells in the prostatic stroma, which was strongly positive for leukocyte common antigen and CD20. CD3, CK, PSA, BCL2, k-light chain, Cyclin D1 and synaptophysin were negative. Histopathology and immunohistochemical profile in the case was consistent with the diagnosis of diffuse large B-cell non-Hodgkin lymphoma of the prostate.