The aim of the present study was to evaluate the ability of Tl-201 abdominal SPECT to differentiate between chronic focal pancreatitis and pancreatic malignancy. Seventeen patients (12 men, 5 women; mean age, 56 years; 9 pancreatic cancer, 8 chronic pancreatitis) with pancreatic mass were prospectively investigated with Tl-201 abdominal SPECT. In all patients, CT and/or US could not clarify the nature of the pancreatic mass. Focal hot uptake was present in 8 of 9 patients with pancreatic cancer, while it was present in 2 of 8 patients with chronic pancreatitis. Therefore, the sensitivity and specificity of the present study were 89% and 75%, respectively. A significant difference of Tl-201 uptakes was noted between benign and malignant masses (p < 0.05). Therefore, we concluded that Tl-201 abdominal SPECT was a useful test in differentiation of malignant from benign pancreatic mass, especially when the differentiation could not be made by other imaging modalities.