The preservation of pathogenic germline mutations in tumor tissues is usually not questioned, while it remains unknown whether these interact with somatic genotypes for patient outcome. Herein we compared germline and tumor genotypes in operable triple-negative breast cancer (TNBC) and evaluated their combined effects on prognosis. We analyzed baseline germline and primary tumor genotype data obtained by Sanger and Next Generation Sequencing in 194 TNBC patients. We also performed multiple tests interrogating the preservation of germline mutations in matched tumors and breast tissue from carriers with available material. Patients had been treated within clinical trials with adjuvant anthracyclines-taxanes based chemotherapy. We identified 50 (26%) germline mutation carriers (78% in ) and 136 (71%) tumors with somatic mutations (83% in ). Tumor mutation patterns differed between carriers and non-carriers (P<0.001); mutations were exclusively present in non-carriers (P=0.007). Germline mutations were not detected in matched tumors and breast tissues from 14 out of 33 (42%) evaluable carriers. Microsatellite markers revealed tumor loss of the germline mutant allele in one case only. Tumors that had lost the germline mutation demonstrated a higher incidence of somatic mutations as compared to tumors with preserved germline mutations (P=0.036). Germline mutation status significantly interacted with tumor mutations for patient disease-free survival (interaction P=0.026): In non-carriers, tumor mutations did not affect outcome; In carriers, those with mutated tumors experienced more relapses compared to those with wild-type tumors (36% vs. 9% relapse rate, respectively). In conclusion, we show that loss of germline mutations is not a rare event in TNBC. This finding, the observed differences in tumor genotypes with respect to germline status and the prognostic interaction between germline BRCA1-related and tumor mutation status prompt for combined germline and tumor genotyping for the classification of TNBC, particularly in the context of clinical trials evaluating synthetic lethality drugs.