Background: Retrospective data suggest that compared to double hormone receptor positive (HR+) (estrogen [ER+] and progesterone receptor [PgR+] positive), single receptor-positive (ER+/PgR- or ER-/PgR+) breast cancer (BC) patients have worse outcomes. Additionally, whether the ER-/PgR+ group is a real phenomenon or an analytic artifact remains elusive. Here, we evaluate the molecular classification and clinical outcomes of single versus double receptor positive BC patients enrolled in the GEICAM/9906 trial. Methods: We analyzed data from the GEICAM/9906 trial, a prospective adjuvant randomized phase-III study comparing six cycles of FEC to four cycles of FEC followed by eight weekly cycles of paclitaxel. HR+ patients received endocrine treatment at completion of chemotherapy. HER2+ patients did not receive adjuvant trastuzumab. Archival tumors were retrieved retrospectively and classified into intrinsic subtypes using the PAM50 gene expression assay. Distant metastasis free survival (DMFS) and overall survival (OS) were explored using a cox proportional hazard analysis Results: Of the 1,246 trial participants, data on intrinsic subtypes by central determination were available for 816 patients, from them 675 were double or single receptor positive. HER2+ disease was more common in the ER+/PgR- group (19%) than in the ER-/PgR+ or ER+/PgR+ groups (each 10%). The luminal A subtype was predominant within the double receptor positive (46%) and ER-/PgR+ (53%) patients. The majority of ER+/PgR- BC were luminal B (49%) or HER2 enriched (31%). Compared to double receptor positive patients, DMFS was similar in ER-/PgR+ patients (HR 1.12, 95%CI 0.52-2.40, p = 0.77), but worse in ER+/PgR- patients (HR 1.59, 95% CI 1.09-2.34, p = 0.02). Similar results were observed for OS (HR 1.39, 95% CI 0.71-2.74, p = 0.34 and HR 1.71 95% CI 1.20-2.74, p = 0.003 respectively). Conclusions: The ER-/PgR+ subgroup resembles double receptor positive disease in terms of distribution of molecular subtypes and outcomes. The poor outcomes of the ER+/PgR- group may be explained by the higher proportion of patients with HER2-positive disease who did not receive adjuvant trastuzumab.