NKT cells are a regulatory T cell lineage shown in mice to promote immunity to tumours. Clinical studies report associations between NKT cell defects and cancer and several clinical trials have targeted NKT cells in patients with solid or hematological malignancies. MAIT cells share many characteristics with NKT cells, including regulatory functions, but their role in human cancer has not been studied in detail. Given this progress, it is surprising that NKT cell defects remain poorly defined in most cancer patient groups due to non-stringent NKT cell identification, superficial analysis of NKT cell function and pooling of data from patients with different cancers and/or treatments (Berzins and Ritchie, Nature Reviews Immunology, 2014). We now report significant defects in NKT and MAIT cell pools of patients with specific forms of cancer, including lung, colorectal and a range of hematological malignancies (including multiple myeloma –Chan et al, Clin Exp Immunol 2014). The ratio between functionally distinct subsets is grossly defective in several of these patient groups and significant functional defects have been identified. Our studies shed new light on the role of NKT and MAIT cells in human cancer and have important implications for NKT or MAIT cell-based therapies that rely on the potential regulatory influence of these cells remaining intact in patients.