Background: PDGF-C has been described in tumor associated fibroblasts, yet little is known about its expression in human breast cancer.Methods: We have generated and characterized a monoclonal antibody (clone 6B3) against human PDGF-C which was used to analyze the expression patterns of PDGF-C in 890 human invasive breast cancer cases.To further explore the molecular mechanism of the clinical data, an orthotopic mouse model using the breast tumor cell line MDA-MB-231 was established.Results: PDGF-C shows a diffuse cytoplasmic immuno-reactivity in epithelial and stromal cells including tumoral capillaries.A gradual increase of expression from normal tissue via in situ carcinomas to invasive cancer was noted.In invasive carcinomas epithelial PDGF-C correlates significantly and positively to tumor grade, CK5/6, Her2 and Ki-67 fraction.Negative significant correlations were noted for ER/PR and menopausal status.In a multivariate survival analysis, PDGF-C was demonstrated as an independent prognostic marker of overall patient survival.In the mouse model, treatment with clone 6B3 inhibited the tumor growth significantly in comparison to the controls and decreased the vessel density in the tumor mass.Conclusions: PDGF-C might play an important role in tumor progression of breast cancer, particularly of basal phenotype.Targeting PDGF-C using monoclonal antibodies may offer a new therapy option for this tumor subgroup.