In French Guiana, a territory characterized by significant sociodemographic and geographic disparities, the incidence of colorectal cancer (CRC) has been poorly documented despite its major public health implications. This study aims to describe the epidemiology of CRC in French Guiana from 2003 to 2017.We analyzed all incident cases of CRC recorded by the French Guiana Cancer Registry between 2003 and 2017. The analysis focused on the distribution of cases by sex, age, and health regions. Age-standardized incidence rates (ASIRs) were calculated, and temporal and spatial trends were examined. A total of 464 cases of CRC were recorded during the study period. The SIR decreased by an average of 3.3% per year, from 20.1 cases to 12.6 per 100,000 person-years. This trend masks opposing dynamics: an average annual decrease of 8.4% among women and an average increase of 2.2% per year among men. The age-specific rate increased by approximately 2.4% per year among those aged 50–64, and an upward trend was observed in the 40–49 age group (+3.3% per year among men, +1.1% per year among women) over the 2003–2017 period. Spatial analysis revealed a high concentration of cases in the Centre Littoral region (88% of cases), with a standardised incidence rate five times higher than that of the Maroni region. These results highlight marked epidemiological contrasts in CRC in French Guiana, particularly by sex and geography. The increase in incidence among men and the high concentration of cases in coastal areas underscore the need to strengthen screening and prevention strategies. Special surveillance is required for early-onset CCR in young adults, an emerging trend that could warrant an adaptation of recommendations in the future.