Retroelements (REs), which function via a “copy-and-paste” mechanism, comprise nearly half of the human genome. The Long Interspersed Nucleic Elements, type 1 (LINE-1 or L1) are the only active autonomous REs. They are able to retrotranspose other RNAs including Alu and SVA REs, and occasionally protein-coding RNAs. Retroelements are silenced via multiple mechanisms, but genomic instability of cancer cells often leads to aberrant disruption of RE repression and enhances their transposition activity. The main goal of our research is to explore RE activity in chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) and to study the impact of therapy and TP53 inactivation on RE activity. To identify tumor-specific RE insertions, we adopted a highly sensitive amplicon NGS protocol for localizing insertions of REs from Alu-Ya5, Alu-Yb8, or L1-HS families into their target genomic regions. In total, 99 samples from 17 MDS and 21 CLL patients, and 60 samples from 4 leukemic cell lines were analyzed.