Although atypical ductal hyperplasia and carcinoma in situ of the pancreas have been well-documented, the natural history and rate of progression of these lesions are unknown. We report two patients, 68 and 52 years of age, who underwent Whipple's procedures for chronic pancreatitis. Histologic sections of the pancreas from both patients showed numerous foci of atypical ductal hyperplasia/carcinoma in situ that extended to the surgical margins of resection. Twenty-nine years after the Whipple's procedure, the first patient had a fine needle aspiration biopsy of a mass in the residual pancreas. The fine needle aspirate and cell block showed a conventional infiltrating ductal carcinoma of the pancreas. Nine years after the Whipple's procedure, the second patient underwent a distal pancreatectomy for a mass involving the body and tail of the pancreas that histologically proved to be a conventional infiltrating ductal carcinoma. These two cases suggest that progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive carcinoma may take many years. This information about the natural history of these lesions may provide impetus for early detection and improved therapy and survival. Specimens of chronic pancreatitis obtained by Whipple's procedure provide surgical pathologists with the opportunity to search and become familiar with atypical ductal lesions of the pancreas not associated with invasive carcinoma.