Background: The detection of CTCs in MBC is associated with worse prognosis and metastases development. We evaluated the integration of immunity biomarkers such as monocyte, neutrophil and platelets LRs (MLR, NLR, PLR) with CTCs data to identify new clues about the interaction between MBC and the immune system. Methods: The study enrolled 44 MBC patients (pts) at the University Hospital of Udine, Italy, between 2013 and 2015, regardless of the line of treatment. CD45^neg circulating cells (CC) were sorted through the DEPArray microfluidic system, based on a multiparametric fluorescence analysis. The CD45^neg CC phenotypes were defined as epithelial (E CTC), mesenchymal (MES) and transitional (EM CTC). MLR, NLR and PLR cut-offs were previously obtained through ROC analysis using propensity score-matched healthy controls (Gerratana et al 2018). The association between LRs and CD45^neg CC was explored through Kruskal Wallis test. CC subtypes were analyzed both as a percentage of total CD45^neg CCs and as absolute values. Results: In luminal-like MBC pts, both NLR and PLR were significantly associated with EM CTC (P = 0.016), while a trend was observed in respect to MLR. In pts with HER2 positive MBC, PLR was significantly associated with E CTC (P = 0.042). Notably, only MLR was associated with EM CTC in the total population (P = 0.02). Pts with visceral involvement had higher EM CTC and E CTC when MLR^high (P = 0.036 and P = 0.031, respectively) and E CTC when PLR^high (P = 0.025), while MES was significantly lower when MLR^high (P = 0.001). In particular, in case of liver localizations, the MLR^high subgroup showed higher E CTC (P = 0.022) and lower MES (P < 0.001). Pts with bone localizations had lower MES when MLR^high (P = 0.004). Interestingly, MLR^high pts with 2 or more sites of distant involvement, had higher EM CTC and lower MES (P = 0.015 and P < 0.001, respectively). Conclusions: MLR is associated with CD45^neg CC subtypes proportions. Particularly intriguing is the direct correlation with EM CTCs suggesting an interlink between CTC and immunity in MBC pathogenesis and progression. Moreover, these findings highlight the need to explore more granular classifications for CD45^neg CC.