Acquired clonal chromosomal abnormalities (CAs) are usually considered to be disease-related. However, when a CA of this type is the only abnormality present (and especially in small clones), the clinical significance is unclear. Here, we review the literature on recurrent CAs whose significance is regularly subject to debate. Our objective was to help with their interpretation and develop guidelines for sex chromosome loss, trisomy 15, trisomy 8, deletion 20q and other isolated non-myelodysplastic neoplasm (MDS)-defining CAs. We suggest that non-MDS-defining CAs correspond to clonal hematopoiesis of indeterminate potential (CHIP) in the absence of cytopenia and clonal cytopenia of undetermined significance (CCUS) in the presence of cytopenia. Lastly, we review the literature on persistent polyclonal binucleated B-cell lymphocytosis; although usually benign, this condition may correspond to a premalignant state.