Colorectal perineuriomas are characterized by a mucosal proliferation of benign stromal cells expressing perineurial markers leading to separation and/or disorganization of the crypts that frequently display a serrated/hyperplastic architecture. Previous studies demonstrated a high prevalence of a BRAF p.V600E mutation in perineuriomas with serrated crypts and suggested that perineuriomas without crypt serration may represent an unrelated, different type of polyp. Yet, these molecular analyses included only 2 cases of perineuriomas without crypt serration. In fact, no previous studies can be found in the literature that have separately analyzed serrated and nonserrated perineuriomas and made a comparison between them. We retrospectively evaluated the clinical, histologic, immunohistochemical, and molecular features of 15 perineuriomas without and 45 with crypt serration (NSPs and SPs, respectively). No significant differences were found between the groups with regard to sex, age, location, and size. Histologically, the perineurial proliferation in SPs and NSPs demonstrated similar features with fascicles or bundles of bland, plump spindle cells surrounding and separating the crypts. All lesions showed expression with at least 2 of 4 perineurial cell markers (epithelial membrane antigen, claudin-1, GLUT-1, and collagen type IV). Molecular analysis performed in 20 cases (8 SPs and 12 NSPs) identified BRAF mutation of codon 600 in 5 (62%) SPs including 3 with p.V600E (c.1799T>A) and 2 with p.V600R (c.GT1798_99GT>AG). In contrast, no case of NSPs harbored BRAF mutations (p value 0.004). Our findings confirm that BRAF mutations originate in the serrated epithelium of SPs and demonstrate that SPs and NSPs have similar clinical and endoscopic characteristics and similar stroma, suggesting that they might represent 2 variants of a single lesion.