Objective To explore the diagnostic values of cytology combined with histopathology in the diagnosis of space occupying pancreatic lesions with endoscopic ultrasound ⁃ guided fine ⁃ needle aspiration（EUS ⁃ FNA）. Methods The data of 51 patients with pancreatic space occupation were collected and all the patients underwent EUS⁃FNA and cytological and histopathological examination. The cytological，histopathological and com⁃ bined diagnosis results were compared with the final diagnosis results，and the application values of different diag⁃ nostic methods was analyzed. Results The sensitivity，specificity and area under curve（AUC）of the cytological examination were respectively 91.11%，100.00% and 0.981. The corresponding values for histopathological exami⁃ nation were respectively 75.56%，83.33% and 0.852. The values of combined detection were respectively 95.56%， 83.33% and 0.987. The diagnostic efficacy of the combination examination was better than that of histopathology （χ2 = 4.55，P = 0.03），and the difference was statistically significant. Conclusion Endoscopic ultrasound⁃guided fine needle aspiration cytology combined with histopathology can improve the diagnostic rate of pancreatic space occupying lesions and is considerably safe.