It is believed that sessile serrated adenomas/polyps lead to the development of microsatellite unstable cancer via a dysplasia-carcinoma sequence. Little is known regarding the morphologic and biologic features, and outcome of sessile serrated adenomas/polyps with dysplasia, or of its specific dysplasia subtypes (intestinal versus serrated). The aims of this study were to analyze and compare the clinical, pathologic, and outcome characteristics of sessile serrated adenomas/polyps with serrated versus intestinal dysplasia. The study included 86 patients with sessile serrated adenomas/polyps with dysplasia (50 serrated dysplasia, 22 intestinal dysplasia, 14 mixed serrated and intestinal dysplasia). The clinical and pathologic features, and the prevalence rate of prior, concurrent, and future neoplastic lesions, were compared between sessile serrated adenomas/polyps with intestinal versus serrated dysplasia and with matched control patients with ≥1 conventional adenoma. The mean age of the patients, polyp size, and prevalence of adenocarcinoma within the polyps were significantly higher in sessile serrated adenomas/polyps with high versus low-grade dysplasia. Sessile serrated adenomas/polyps with intestinal dysplasia showed a significantly higher rate of adenocarcinoma (23%) compared with those with serrated dysplasia (6%, P=0.05), and the high-grade lesions occurred at a significantly younger age in the former compared with the latter (65 versus 76 years, P=0.05). Compared with patients with conventional adenomas, patients with sessile serrated adenomas/polyps with dysplasia showed a significantly higher rate of invasive carcinoma within the polyps (12 versus 0%, P=0.01) and a significantly lower association with prior or future conventional adenomas. Sessile serrated adenomas/polyps with dysplasia should be considered high-risk neoplastic precursor lesions, particularly those with intestinal dysplasia. Cancer may develop from sessile serrated adenomas/polyps with either type of dysplasia.