The high proportion of atypical CLL/SLL patients, high incidence of MYD88 and KMT2D variants, and significant correlation between MYD88 variants and atypical immunophenotypes suggested that in addition to classic diagnostic and prognostic assessment systems, more comprehensive population-related characteristics should be taken into consideration in the clinical diagnosis, management, and treatment strategies of CLL/SLL. This evidence concerns the gene MYD88 and B-cell chronic lymphocytic leukemia.