e15605 Background: Adenocarcinoma in situ (pTis) of the colon is defined as malignant cells confined within epithelium or mucosa. Since pTis is not invasive, polypectomy alone is usually adequate, especially if resection margins are cancer-free. We performed a population-based study to investigate the association of intrapolyp pTis and subsequent colon cancer. Methods: We queried the SEER database (1975-2017) for patients with pTis in adenoma. We further filtered patients with subsequent colon cancers. Standard incidence ratios (SIRs) were used to evaluate the excess risk of developing subsequent colon cancers comparing to the general population. Difference between patients who did or did not develop colon cancer were analyzed using Chi-square test. Results: A total of 15164 patients with pTis were identified. Among them, 736 (4.85%) patients developed subsequent colon cancer. Age ≥70 years, pTis in villous adenoma, polyp in hepatic flexure, splenic flexure, transverse colon, descending colon, and diagnosis year before 2000 were associated with increased risk of developing subsequent colon malignancy (all p< 0.05). Polypectomy comparing to colectomy (total, subtotal or partial) is associated with a higher rate of developing subsequent colon cancers ( p < 0.05). In patients with intrapolyp pTis, observation/expectation (O/E) of developing colon cancers are elevated to 4.76, 1.84, 1.66, and 1.28 within one year, 1-5 year, 5-10 year, and after ten years, respectively (all p< 0.05). O/E for the male and female is 1.80 and 1.63 (both p< 0.05); for the white and black is 1.64 and 2.21(both p< 0.05). Conclusions: Subsequent colon cancers developed in 4.85% of pTis patients. Excess risk of developing subsequent colon cancers is highest in the first year, and declines with time but persists beyond ten years. Male and black have the highest excess risk. Factors like older age, villous adenoma, location from hepatic flexure to descending colon, and polypectomy are associated with developing subsequent colon cancers.