Research investigators have shown a growing interest in investigating alterations underlying skeletal muscle wasting in patients with cancer. However, skeletal muscle dysfunctions associated with cancer cachexia have mainly been studied in preclinical models. In the present review, we summarize the results of clinical studies in which skeletal muscle biopsies were collected from cachectic vs. non‐cachectic cancer patients. Most of these studies suggest the presence of significant physiological alterations in skeletal muscle from cachectic cancer patients. We suggest a hypothesis, which connects structural and metabolic parameters that may, at least in part, be responsible for the skeletal muscle atrophy characteristic of cancer cachexia. Finally, we discuss the importance of a better standardization of the diagnostic criteria for cancer cachexia, as well as the requirement for additional clinical studies to improve the robustness of these conclusions.