Herein, as we explore the potential of MinION technology as a new approach in the clinical routine for short-fragment sequencing, we used a substantial cohort of 164 samples, previously characterized using NGS or Sanger sequencing, targeting 15 genes with diagnostic, prognostic, or therapeutic relevance in MPN (CALR, JAK2, MPL, CSF3R, SETBP1), MDS (SF3B1), AML (NPM1, KIT, IDH2, IDH1, CEBPA, NRAS, KRAS, and TP53) and CML (ABL1). The gene discussed is NPM1; the disease is acute myeloid leukemia.