Data on colorectal cancer (CRC) in HIV-positive patients are limited. The objective of this study was to investigate the incidence, presentation, and outcome of CRC in HIV patients. Clinical data on patients diagnosed with CRC and concurrent HIV/AIDS infection between 1994 and 2003 were retrieved from the institutional records. Each identified patient was randomly matched with two HIV-negative CRC patients based on age, sex, race, and TNM stage at cancer diagnosis. Presentation, treatment toxicities, recurrence, and overall survival rates were assessed. Data were further compared with those of the published international Surveillance Epidemiology and End Results (SEER) data. Out of 3,951 CRC patients, 12 HIV CRC patients (0.3%) were identified. Median age at cancer diagnosis was 41 years (29-52), revealing a 3:1 ratio between patients younger and older then 50 years, compared to a 1:33 ratio in the general population. Compared to 57% in the general population, 90% of the patients had advanced stages (III-IV) at diagnosis. The median follow-up time for both cases and controls was 30 months (6-65). HIV-positive patients had a shorter disease-free survival than the controls. No difference in overall survival was demonstrated, however survival was significantly reduced in the HIV-positive patients when only patients who were initially disease-free were compared. Adjuvant therapy was well-tolerated in all patients without chemotherapy-related deaths. HIV-positive CRC patients tend to have an early and more aggressive presentation with less favorable outcome. Further epidemiology studies to refute or accept our observations may suggest a reduced threshold for screening for CRC in HIV-positive patients.