Background: The 2011 St Gallen guidelines recommend the use of Ki67 as a surrogate marker for luminal A and Luminal B breast cancer subtypes. Pts with luminal B subtypes should be treated with adjuvant chemotherapy. The guidelines also recognize the Oncotype DX RS as a predictor of chemotherapy benefit. The aim of this study is to assess the distribution of the RS in luminal A and luminal B breast cancer subtypes as defined by Ki67. Methods: Data from 131 pts with invasive breast cancer for which Oncotype DX results and pathology data were available. Pathological assessment was evaluated by the same pathologist. Estrogen (ER) and progesterone (PR) receptor was assessed by immunostaining (cut-off 10% nuclear staining). Ki67 was assessed by IHC [high (≥14%) and low (< 14%)]. Histological grade was performed by using Nottingham grading system. Results: Median age: 50 (range: 35-78); premenopausal status: 53 pts (44.2%). Median tumor size: 1, 5 cm (0, 3-5); Median of Ki 67 index: 15 (range: 3-63); 79 pts (66.4%) had negative-lymph nodes. Seventy (58.3%) tumors were classified as Luminal B (Ki 67 ≥14%) and 50 (41.7%) as Luminal A. Grade III were more common in Luminal B 14 (20.3%) than in Luminal A 1 pts (2%) patients (p=0.003). Chemotherapy was the first recommendation in 29 pts (41.4%) with Luminal B vs. 7 pts (14%) with Luminal A; hormonotherapy was the first recommendation in 32 pts (45.7%) with Luminal B and 37 pts (74%) in Luminal A (p =0.003). In the Luminal B group, Recurrence Score results was low in 42 (60%) pts, intermediate in 19 (27.1%) and high in 9 (12.9%) while in the Luminal A group 31 (62%) had low; 16 (32%) intermediate and 3 (6%) high Recurrence Score results (p=0.433). RS changed the first treatment recommendation in 35 (50%) cases of Luminal B subtype vs. 14 (28%) cases in Luminal A subtype (p=0.016). Conclusions: The results show that a substantial number (60%) pts with Luminal B breast cancer subtype had a low RS, therefore preserving them from adjuvant chemotherapy treatment. The wide range of RS in both Luminal B and Luminal A breast cancer subtypes confirm the important role of Oncotype DX in treatment decision making.