Here, we collected in cellulo, in vitro, and in silico evidence for the role of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1, better known as CD38, in binding and restraining extracellular cGAMP in a model of human multiple myeloma (MM), a malignant neoplasm characterized by a typically high expression of CD38. Here, CD38 is linked to plasma cell myeloma.