In biomarker discovery and classification field, the size of the model is a crucial aspect. The model should be built avoiding over-fitting but preserving generalization, in terms of capability to correctly classify new subjects. In this study we limited the clusters to no more than 20 features. Initially we focused on the possibility to distinguish benign renal masses or healthy subjects from malignant tumours and a classifier with twelve urinary peptides with an AUC of 0.89 was generated. Then, we afforded the possibility to discriminate ccRCC patients from healthy subjects and a classifier with twelve peptides was selected with good discriminating capability that were confirmed in an independent cohort of subjects with an AUC of 0.96. Identity of seven of the ions included in the clusters were obtained by MALDI-TOF/TOF and by nLC-ESI-MS/MS analysis. Most of them were different from those identified by CE-MS and used in the model by Frantzi et al. and, interestingly, most of them were correlated to the presence of a tumour mass. This is not surprising since the data on urinary peptidome delivered from different pre-fractionation of sample and from a different chromatographic separation provide complementary information. Hereby we describe two patterns of twelve urinary peptides with a high discrimination power obtained by an SVM-based statistical approach. Seven of these signals were most likely identified. In particular, two ions at m/z 1670 and 2216 observed in MALDI-LM spectra were identified as fragments of the human glycoZ-VAD-FMK protein uromodulin and they were present in higher concentration in patients affected by both ccRCC and other malignant kidney tumours. The urinary excretion of UMOD has been studied in various physio-pathological states, but its precise biological role is still undefined. Clinical relevance of this protein has been described in several pathologies and THP mutations have been associated with chronic kidney disease, altered glomerular filtration rate and decreased urinary excretion. Furthermore, decreased UMOD expression has been observed in end-stage renal disease, in kidney neoplasms and in cysts from autosomal dominant polycystic kidney disease. Moreover it was also reported with a lower abundance in other pathologies like renal calculi disease, IgA nephropathy or diabetic nephropathy. The relative concentration of two urinary UMOD fragments, at m/z 1912 and 1824, included in a discriminant model able to distinguish RCC patients from controls in our previous pilot study, was confirmed by our findings. In a peptidome profiling study on urine samples from healthy subjects exposed to high altitude hypoxia another UMOD peptide, Val592IDQSRVLNLGPITArg606, a few amino acids shorter than fragments identified in this study, was also detected as altered in urinary levels. The ion at m/z 2659 was identified as a fragment of fibrinogen alpha chain and was found highly represented in the urine of patients.