We report three examples of either localized or segmental adenomyomatous hyperplasia of the gallbladder in association with cholelithiasis. Two patients were women, 58 and 81 years of age, and the third was a 62-year-old man. The finding of perineural invasion by epithelial ductal structures in two cases and of perineural and intraneural invasion in the third case led to initial diagnoses of well-differentiated adenocarcinoma. The presence of mucinous metaplasia in some of the cystically dilated ductal structures and the diffuse proliferation of pyloric-type glands probably contributed to the erroneous diagnosis of adenocarcinoma. Although the mechanism by which the epithelial structures invade perineural spaces is unknown, we offer two possible explanations: (1) extension and growth of epithelial ductal structures along tissue planes of least resistance, such as the perineural space, and (2) growth of hyperplastic nerve trunks in close proximity to or within epithelial structures. The pattern of perineural invasion in cases of adenomyomatous hyperplasia should not be confused with adenocarcinoma. Attention to the general architecture of the lesion and the bland cytologic features of the glands and ductal structures should prevent this misinterpretation. The gallbladder should be added to the list of organs in which perineural invasion by benign epithelial structures has been described.