Hepatocyte nuclear factor-4α (HNF4α) is a member of the nuclear receptor superfamily is critical for the maintenance of epithelial cell function and normal colon physiology. Isoforms of HNF4α are generated by alternative splicing of the P1 and P2 promoter.  Isoforms of HNF4α 1-6 originate from P1 promoter while HNF4α 7-12 are derived from the P2 promoter. The P1 and P2 proteins differ in approximately 16-29 amino acids in the N-terminal domain.  HNF4α is critical for the balance between proliferation and differentiation. In normal tissues, HNF4α P1 is localized to the nucleus and expressed in the small intestine, colon, liver, and kidney, but no expression was found in stomach and lung. HNF4α P1 may be used to identify metastatic tumors to the lung. In gastric carcinomas, intestinal, mixed and null types showed HNF4α P1 positive, but the gastric type was HNF4α P1 negative. In contrast, HNF4α P2 was expressed in all gastric carcinomas. HNF4α P1 antibody may be useful for subclassification of gastric tumors.   In several studies focusing on colorectal carcinoma, HNF4α P1 was shown to be frequently lost in tumor cells. In contrast, HNF4α P2 expression was unaffected.