Cancer is a disease characterized by dysregulation of metabolism and cellular energetics, crucial requirement for tumour initiation and progression. Systemic and local metabolic changes in cancer are supported by gene mutations, epigenetic modifications, impaired expression of metabolism-related receptors and enzymes, and ultimately lead to the altered levels and ratio of metabolites in tissues and biological fluids. Traces of certain molecule caused by metabolic changes in bodily fluids and exhaled breath of cancer patients provide the foundation for the identification of novel metabolism-related targets enabling non-invasive diagnostic approaches. The review of clinically oriented papers published in the last two decades raised various lists of cancer-associated volatile organic compounds (VOCs) derived by the comparison of the global metabolic profiles of breath or biological fluids such as blood, urine, saliva and sweat from cancer and cancer-free subjects. The anatomical sites were lung, esophagus, stomach and colon, whereas the most represented chemical classes were hydrocarbons (including both aliphatic and aromatic), followed by alcohols, aldehydes and carboxylic acids. Gas chromatography-mass spectrometry (GC-MS) was the primary platform used for the analysis of the human volatome. Studies on cancer-associated VOCs analysed in cell cultures or animal models are underrepresented compared to more translational works based on the study of real samples, mainly due to lack of a dedicated technology. Overall, the current scientific evidence suggests the presence of a complex and significant pattern of VOCs in the volatome of cancer patients that needs to be deciphered. The molecular characterization and the comprehension of the biological role of cancer-related VOCs in breath, biological fluids and tissues will represent an invaluable clinical opportunity to develop non-invasive tests for early detection and monitoring of cancer.