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Simple Summary Renal cell carcinoma (RCC) is often late diagnosed at an advanced stage, worsening the prognosis of the patients. Thus, an early marker is desirable. This paper presents an innovative combined approach useful to identify, for the first time, the presence of LOX-1 protein within the urine of clear cell RCC patients. The LOX-1 protein is related to metabolic disorder-associated carcinogenesis and is shown to be quantitatively correlated to tumor grade and stage. The analysis of volatile compounds released by urine shows the diagnostic potentialities of volatilome and indicates that at least one volatile compound is correlated with both LOX-1 and cancer. In this work, we propose the potential use of a noninvasive approach that enables an early, routine ccRCC diagnosis and leads to a better management of the patients. Abstract Renal cell carcinoma (RCC) represents around 3% of all cancers, within which clear cell RCC (ccRCC) are the most common type (70–75%). The RCC disease regularly progresses asymptomatically and upon presentation is recurrently metastatic, therefore, an early method of detection is necessary. The identification of one or more specific biomarkers measurable in biofluids (i.e., urine) by combined approaches could surely be appropriate for this kind of cancer, especially due to easy obtainability by noninvasive method. OLR1 is a metabolic gene that encodes for the Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), implicated in inflammation, atherosclerosis, ROS, and metabolic disorder-associated carcinogenesis. Specifically, LOX-1 is clearly involved in tumor insurgence and progression of different human cancers. This work reports for the first time the presence of LOX-1 protein in ccRCC urine and its peculiar distribution in tumoral tissues. The urine samples headspace has also been analyzed for the presence of the volatile compounds (VOCs) by SPME-GC/MS and gas sensor array. In particular, it was found by GC/MS analysis that 2-Cyclohexen-1-one,3-methyl-6-(1-methylethyl)- correlates with LOX-1 concentration in urine. The combined approach of VOCs analysis and protein quantification could lead to promising results in terms of diagnostic and prognostic potential for ccRCC tumors.