THP-1 is a representative leukemia cell line and is registered with four different numbers in JCRB and RIKEN BRC cell banks. However, differences between these four lines remain unclear. In our study, these four THP-1 cell lines, JCRB0112, JCRB0112.1 (corresponding to ATCC TIB-202), RCB1189 (DSMZ ACC-16) and RCB3686, have been compared at chromosome and DNA sequence levels. Our results reveal that ploidy has been changed in JCRB0112 and RCB1189, which are triploid and tetraploid, respectively. Patterns of variant frequencies from target sequencing are unique to each ploidy, estimating whole genomic status based on partial sequence data. SNP microarrays showed four distinct profiles with a large-scale loss of heterozygosity, reflected in subtle differences in STR genotypes. Transcriptome patterns suggest that JCRB0112.1 has diverged highly from the other three lines. RCB1189 and JCRB0112.1 responded to PMA faster than RCB3686 and JCRB0112. We have identified RCB3686 as the closest to the original THP-1, which can be an optimal model of AML-M5. These four THP-1 genomes and transcriptomes exhibit significant differences, indicating four independent sublines and demonstrating the influence of genetic drift on gene expression. As these cells share the same name, THP-1 must be accompanied by their registration number of each cell repository. Our data provide genomic features of four THP-1 sublines and serve as a reference profile to classify widely spread THP-1 progenies, which could be distinguished by a comparison of 24 STR markers. Multiple sublines can be generated by separate cell cultures, which would be explained by in vitro branched evolution.