INTRODUCTION: Primary colorectal lymphoma occurs infrequently, representing only 0.3% of colonic malignancies and 3% of gastrointestinal lymphomas. Follicular lymphoma typically presents with painless peripheral adenopathy in the cervical, axillary, inguinal and / or femoral regions with rare gastrointestinal (GI) involvement. If GI involvement occurs, the small bowel is most often involved. We report a rare case of follicular lymphoma in the colon discovered during a screening colonoscopy in a patient with HIV. CASE DESCRIPTION/METHODS: A 56-year-old male with history of well-controlled HIV (CD4 476) was referred for colon cancer screening. The patient was in good health and denied GI complaints including diarrhea, constipation, melena, hematochezia, abdominal pain, and involuntary weight loss. He had no family history of colon cancer. His screening colonoscopy revealed a 2-cm polypoid rectal lesion that was 5-cm from the anal verge and a 3-4 cm erythematous polypoid rectal lesion that was 15-cm from the anal verge. Multiple biopsies of both lesions showed atypical follicular hyperplasia with no evidence of lymphoma. A CT and MRI for staging were negative for metastases. A flexible sigmoidoscopy with biopsies showed a focal variably dense nodular lymphoid aggregate composed of CD20-small B cell lymphocytes, positive for BCL2 and negative for CD5, CD10, BCL6, CD43, cyclinD1 and CD23. There was, again, no diagnosis of lymphoma. Another opinion from NIH revealed the specimens to be negative IGH PCR but positive IgK. FISH for BCL2 rearrangement was positive in 65% of the cells. The findings were consistent with follicular lymphoma. He was referred to oncology for further management. DISCUSSION: Colorectal follicular lymphoma is an exceeding rare malignancy. It generally has an indolent course with a good prognosis. Patients with HIV have an increased risk for development of follicular lymphoma, but it is not an HIV-defining diagnosis. Awareness of potential GI complications, including bleeding, intestinal obstruction and perforation, is critical. Further studies are needed to establish management guidelines for colorectal follicular lymphoma in HIV and non-HIV patients.