Objective To summarize the experience of imaging misdiagnosis in patients with ductal adenocarcinoma of pancreas (DACP), to investigate the reasons of misdiagnosis and improve the imaging diagnosis of DACP. Methods The 51 patients who were misdiagnosed by imaging in this study included 13 men and 38 women, with ages ranging from 37-79 years old and the median being 54 years old. All patients underwent CT and MRI examination before they were confirmed as DACP by pathological examination after surgery. The imaging data and pathological results were reviewed and the reasons of misdiagnosis were analyzed. Results Twenty poorly differentiated DACP without cysts were misdiagnosed as "cystic tumor of pancreas" or "pancreatic cyst" due to no obvious enhancement in images; 16 cases of DACP associated with pseudocysts were misdiagnosed as "pancreatitis associated with pseudocyst" due to that the tumors were masked by pseudocysts; and 15 cases of DACP associated with obstructive pancreatitis were misdiagnosed as "focal pancreatitis" due to the tumors' small volume and pancreatitis mask. Indefinite-edge masses which documented no or slight enhancement were seen in all cases (100%); 43 cases (84%) documented the dilated main pancreatic duct were "interrupted"; and 100% of bile ducts were blocked by masses located in the pancreatic head. Conclusion Knowing the local anatomy of pancreas and histopathological features of DACP and understanding imaging characteristics of the secondary changes of DACP can help to avoid imaging misdiagnosis.