Background & Aims: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. Methods: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. Results: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28–5.17; P <.001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58–8.22; P <.001), pancreatic cancer (HR, 6.45; 95% CI, 2.02–20.64; P =.002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76–119.47; P =.013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53–20.23; P =.20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02–3.50; P =.042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. Conclusions: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.