Foamy gland adenocarcinoma is a variant of pancreatic ductal carcinoma, whose precursor has not been described. We describe here the morphologic and immunohistochemical features of the pancreatic intraepithelial neoplasia (PanIN) lesions associated with invasive foamy pancreatic adenocarcinoma. The staining properties and morphologic and immunohistochemical features of 3 foamy PanIN lesions were compared with those of 7 pancreatic foamy gland adenocarcinomas. Hematoxylin and eosin, Mayer mucicarmine, periodic acid-Schiff, and Alcian blue stains were available for review in all cases. Immunohistochemical labeling for cytokeratin (CK)7, CK20, carcinoembryonic antigen polyclonal, MUC1, MUC2, CDX2, p53, and cyclin D1 was performed. The PanIN-1 lesions were found in the nonneoplastic pancreas and were similar to the PanIN-1 lesions of ordinary pancreatic ductal carcinoma. The PanIN-2 and -3 lesions were recognized immediately adjacent to or within the invasive foamy gland carcinoma. In these lesions, small or markedly dilated ducts were lined by cuboidal and columnar dysplastic nonfoamy cells and foamy cells. Hobnail cells were present in 2 cases. The PanIN-1, 2, and 3 lesions and the invasive foamy gland adenocarcinomas stained with mucicarmine, periodic acid-Schiff, and Alcian blue. The 3 PanIN-2 and -3 lesions and all 7 invasive foamy adenocarcinomas labeled with CK7, carcinoembryonic antigen polyclonal, and MUC1, whereas only 2 PanIN-2 and -3 lesions and 5 invasive adenocarcinomas showed immunoreactivity for cyclin D1 and p53. Three distinctive foamy PanIN lesions were identified within 7 invasive foamy gland pancreatic adenocarcinomas. The gradual progression of cytological and architectural abnormalities of the PanIN lesions from PanIN-1 to PanIN-3 excludes neoplastic ductal spread. These foamy PanIN lesions probably represent cancer precursors.