Background: Male breast cancer (MBC) is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry (IHQ) as a luminal disease. In this study, we use for the first time the PAM50 signature to unravel the molecular genetic heterogeneity in MBC. Methods: We collected surgical specimens of invasive MBC from four different Spanish pathology laboratories. IHQ staining for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR) and Ki-67 was performed on tissue microarrays composed of 3 cores sized 0.6 mm per case by standard methods. Breast cancer molecular subtypes were classified according to Cheang et al. (2009). Gene-expression profiling was performed on a research-use-only (RUO) nCounter Analysis System using the RUO PAM50 assay analyzed with the Prosigna algorithm. We explored the association of IHQ and PAM50 subtypes using Fisher’s exact test. Results: From the 78 selected patients, 59 (76%) had enough tumor tissue to be classified by both IHQ and PAM50 approaches. The characteristics of our cohort are the following: mean age 63, tumor-size > 2cm 54%, grade 1 46%, positive lymph nodes 44%, adjuvant chemotherapy (CHT) 51%, hormonotherapy (HT) 80%, CHT+HT 41%. By IHQ these samples are mainly RE, RP and RA positive (97%, 86%, and 90% respectively); HER2, CK5/6 and EGFR negative (100%, 97% and 80%) and with a balanced Ki67 expression (Ki67 > 14 56%). When subtyping by IHQ and PAM50, the majority of samples are luminal B (54 and 63%, respectively) followed by luminal A (43% and 32%). Only 3% by IHQ and 5% by PAM50 are non-luminal (1 basal-like and 1 non-basal triple negative by IHQ and 3 Her2-enriched by PAM50). We found a strong association between both IHQ and PAM50 classifications (p-value = 0.007). Conclusions: In contrast with female breast cancer in which a third of the cases are non-luminal, our findings suggest that MBC is mainly a genomic luminal disease. More research is needed to identify the reason for the scarcity of non-luminal subtypes in MBC and the predominance of the luminal B subtype.