Little is known about gastric neoplasms arising from hyperplastic polyps (HPs).To investigate the risk factors associated with neoplasms within HPs and to evaluate the role of alterations of the p16-cyclin D1-pRb pathway in the malignant transformation of HPs.Retrospective, case-control study.Tertiary-care center.Between May 1995 and January 2011, a total of 809 HPs >1 cm were investigated. Associated neoplasms were present in 30 HPs (case group); 30 HPs without neoplasms were selected as a control group.Gastric polypectomy.The risk factors associated with neoplasms within HPs and immunohistochemical expression of p16, cyclin D1, p53, and Ki-67 between case and control groups.Of the 809 HPs, 15 had associated dysplasia, and 15 had carcinoma. Multivariate analysis showed that neoplasm was associated with patient age (odds ratio [OR] 1.159; 95% confidence interval [CI], 1.243-2.044; P < .001), polyp size (OR 1.103; 95% CI, 1.055-1.152; P < .001), and polyp lobulation (OR 4.549; 95% CI, 1.759-11.0766; P < .001) but not with location, multiplicity, intestinal metaplasia, growth pattern, or Helicobacter pylori infection. Loss of p16 expression and high Ki-67 expression were observed in dysplastic areas of HPs compared with the control group (p16 = 14.3% vs 60%; P = .001, Ki-67 = 60.7% vs 36.7%; P < .001). However, no significant differences were found in nondysplastic areas in both groups.Single-center, retrospective study.HPs >1 cm may indicate the presence of neoplasms. Loss of p16 and high Ki-67 expression may be markers of HP-associated dysplasia.