Regional portal hypertension (RPH) is a clinical syndrome caused by stenosis or occlusion of the splenic vein. It is a rare yet life-threatening cause of upper gastrointestinal bleeding, but it is also the only type of portal hypertension that can be cured. Pancreatic diseases are the most common cause of RPH, and isolated gastric varices represent the characteristic clinical presentation. For patients with gastrointestinal bleeding with normal liver function and unexplained splenomegaly, the possibility of RPH should be considered. The clinical manifestations of RPH are relatively insidious, and are similar to those of portal hypertension caused by liver cirrhosis. Due to insufficient knowledge of RPH, it is more likely to be misdiagnosed clinically. The diversity of primary diseases results in the diversification of the clinical manifestations of RPH, which complicates the diagnosis of the disease. For patients with atypical clinical manifestations, specific auxiliary examinations can be applied to assist in the diagnosis. In terms of the treatment, the primary diseases should be attached the most importance to, and individualized therapies should be provided. The prognosis of RPH is mainly related to the condition of primary diseases, and benign lesions may herald a good prognosis yet malignant lesions a poor prognosis.