Primary adenocarcinoma of the vermiform appendix is a rare entity and is frequently discovered by the pathologist following appendectomy for suspected appendicitis.We present a 42-year-old male with primary mucinous adenocarcinoma of the appendix initially presenting symptoms of acute appendicitis. Histological investigation of the appendectomy specimen showed a mucinous adenocarcinoma and the patient was treated by secondary right hemicolectomy giving the final histopathological classification of an UICC IIIC tumor. Since the patient fulfills the revised Bethesda criteria analysis of immunoreactivity of DNA mismatch repair proteins was performed showing loss of MLH1 and MSH2 expression associated with high microsatellite instability (MSI-H), not yet reported for primary mucinous appendiceal carcinoma. Further genetic analysis for DNA mismatch repair gene mutations were negative. The patient received intensified adjuvant chemotherapy according to the FOLFOX-4-scheme, since MSI-H colorectal carcinomas might show lower response rates following standard 5-FU-based adjuvant chemotherapy.