At present it is unclear whether the mutations are causative of DLCBL/multiple myeloma or are involved in the disease progression but we propose that future research on these diseases takes into account the role of the actin cytoskeleton, especially the RHOA-signaling axis and ACTB mutations in DLCBL patients, and ACTG1 mutations in multiple myeloma patients. Here, RHOA is linked to AL amyloidosis.