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To improve the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), the diagnosis of early-stage PDAC is essential. In particular, the diagnosis of high-grade intraepithelial pancreatic neoplasia/carcinoma in situ (HG-PanIN/CIS) is the best option. However, it is almost impossible to directly observe HG-PanIN/CIS. Thus, identifying a secondary imaging finding due to the disorder is important. Focal pancreatic parenchymal atrophy (FPPA) and hypoechoic area have been reported as preferred secondary signs. We studied 50 patients to clarify the effectiveness of FPPA in diagnosing HG-PanIN/CIS. Most patients had the opportunity to undergo further examination due to the presence of a cyst. Among the 50 patients, 23 (46%) had positive results for serial pancreatic-juice aspiration cytologic examination (SPACE), which has high sensitivity and specificity for diagnosing PADC; 20 of the 23 (87.0%) patients underwent surgery to resect the pancreatic part including the FPPA. Distal pancreatectomy and pancreatoduodenectomy were performed in 19 patients and one patient, respectively. In 13 of the 20 (65%) patients, histopathological examination revealed HG-PanIN/CIS in the pancreatic ductal epithelium of the resected specimens. FPPA could indicate HG-PanIN/CIS, but not satisfactorily. One of the factors for the unsatisfactory results might be the difficulty in identifying FPPA in the pancreatic head area. On the other hand, a pancreatic cyst, especially in the area of FPPA, could lead to the diagnosis of HG-PanIN/CIS. The size of the cyst does not affect the diagnosis of HG-PanIN/CIS.