Background: CD146, a member of the immunoglobulin superfamily, is mainly expressed at the endothelial junction. The soluble form of CD146 is increased in the serum of patients with chronic renal failure. The aim of the study was to investigate CD146 expression on biopsies of normal kidney and nephropathies. Methods: We did an immunohistochemical analysis of 10 normal renal tissues and 126 patients with nephropathies. Results: The mean age of the patients was 47.5 ± 18 years with 65% of men. At the time of the biopsy, 73 patients (57.9%) had a renal failure and the mean proteinuria was 3.3 ± 2.9 g/24 h. Inflammatory syndrome was present in 60 (47.6%) patients. Fibrous interstitial changes from minimal lesions to diffuse lesions were seen in 105 (83.3%) biopsies; the mean glomerulosclerosis index was 16.9 ± 19.7%. Normal kidneys showed CD146 staining on endothelial cells, smooth muscle cells, and mesangium. Normal tubular cells were not stained. If endocapillary proliferation was present, the mesangial CD146 expression was higher. This mesangial expression correlated with proteinuria (p = 0.007) and not with renal failure (p = 0.07). A de novo expression on tubular cells was found in 53 patients (42%) and this expression correlated with age (p < 0.001), male sex (p = 0.04), glomerulosclerosis (p < 0.001), interstitial fibrosis (p < 0.001), and renal failure (p < 0.001). Conclusion: Renal CD146 expression is of interest for determining the pathogenesis of mesangial alterations during glomerular injuries and of tubular phenotypic changes during chronic renal failure.