Abstract Multiple myeloma embodies the paradigm of the deeper the response, the longer the survival. However, results are conflicting regarding achievement of complete remission (CR) and minimal residual disease (MRD) negativity; some patients with persistent M protein have undetectable MRD. We reviewed the frequency of this discordance and outcomes of these patients. We spotlight possible explanations for and consequences of conflicting response criteria and suggest that MRD be assessed in patients achieving very good partial response or better in clinical trials.