Increased HER2 expression has a prognostic, and predictive value in many solid cancer types, predominantly in breast cancer. However the effects of HER2 on survival from cancers of pancreas, gall bladder, cholangiocellular, and ampullary region are not known. In this study, the effects of increased HER2 expression on these types of cancer have been analyzed. Immunohistochemical HER2 staining was performed in 31 (44.9 %) female, and 38 (55.1 %) male patients with a mean age of 65 ± 10 years, and various parameters, mostly survival rates of patients with pancreas (n = 30; 43.5 %), gall bladder (n = 17; 24.6 %), cholangiocellular (n = 12; 17.4 %), and ampullary region (n = 10; 14.5 %) carcinomas were evaluated. Strong (3 +) membranous staining for HER2 was observed in 2 patients with gall bladder cancers (11.76 % of all gall bladder cancers). In 2.90 % of all cases strong membranous staining (2+ or 3+) was observed. Weak (1+) membranous staining was noted in one (3.33 %) pancreatic, and one cholangiocellular (8.33 %) cancer patient, and in none of the ampullary region patient membranous staining for HER2 was observed. Since only scarce number of patients demonstrated membranous staining for HER2, survival analysis was not performed on these patients. Based on cytoplasmic HER2 staining scores, the patients were divided into weakly (0-3 pts; n = 17 patients; 24.66 %), moderate (4-5 pts; n = 22; 31.88 %), and strongly (6-7 pts; n = 30; 43.46 %) stained groups. Patients whose specimens demonstrated borderline statistical significant (p = 0.052) low staining for HER2 had higher survival rates when compared with other cases. Increased HER2 expression has no prognostic, and predictive value in cancers of pancreas, biliary tract, and ampulla vateri. If HER2 will be evaluated in these types of cancer, membranous, as well as cytoplasmic staining properties should be taken into account.