Over the last decade or so, NOTCH and FBXW7 mutations have been reported in a wide range of tumors, such as pediatric and adult T‐cell acute leukemia (T‐ALL), diffuse large B‐cell lymphoma (DLBCL), splenic marginal zone lymphoma (SMZL), Hajdu‐Cheney syndrome, breast cancer (BC), non‐small‐cell lung carcinomas (NSCLCs), etc. Given the array of pathological events, which may be driven by a deregulated FBXW7‐NOTCH interactome in tumors, it is imperative to understand such disease‐critical interactions with a therapeutic perspective in mind.13 The gene discussed is FBXW7; the disease is splenic marginal zone lymphoma.