Juvenile Myelomonocytic Leukemia (JMML) is a rare myeloproliferative neoplasm of childhood characterized by infiltration of abnormal myelomonocytic cells in peripheral blood, bone marrow, and spleen. The majority of JMML patients have somatic and/or germline variants in RAS signaling pathway genes. Although the karyotype is predominantly normal, monosomy of chromosome 7 is observed in about 25% of cases. The diagnosis of JMML can be made by combining clinical, laboratory, and molecular data. In this study, we report the case of a six-year-old male patient with an initial presentation of rectal bleeding accompanied by severe thrombocytopenia. The bone marrow examination showed a mildly hypercellular bone marrow with moderate dysgranulopoiesis and blasts with myeloid characteristics, 1.6% basophils, 3.4% monocytes, and 3.4% promonocytes, suggesting Myelodysplastic Syndrome (MDS) or JMML. Immunophenotyping of peripheral blood revealed signs of granulocytic dysplasia, monocytosis (11.7%), 3.5% promonocytes, and 6.0% immature myeloid cells, which were also suggestive of MDS or JMML. Hemoglobin electrophoresis revealed 13.6% fetal hemoglobin. Bone marrow biopsy showed a cell-to-fat ratio of 98% due to the proliferation of blastoid immature cells. No fibrosis or deposits were observed in the bone marrow. Karyotyping of the bone marrow was normal, and BCR:ABL1 fusion was negative. Next-Generation Sequencing (NGS) panel testing was performed to detect variants in 40 genes (including CBL, KRAS, NRAS, PTPN11, and NF1) and gene fusions involving 29 driver genes. Variants were detected in the PTPN11 gene (c.215C>T, p.Ala72Val, VAF: 42.7%) and NRAS gene (c.35G>A, p.Gly12Asp, VAF: 28.9%), both of which are RAS pathway genes. No gene fusions were detected. Somatic variants in PTPN11 are the most common molecular alterations in JMML, detected in 35% to 40% of patients, and are associated with an aggressive clinical course and adverse prognosis. Approximately 25% to 30% of patients have somatic variants in NRAS or KRAS. The current diagnostic criteria for JMML include blast percentage in peripheral blood or bone marrow less than 20%, splenomegaly, monocyte count ≥1.0×109/L, absence of BCR:ABL1 fusion, and the presence of at least one variant in RAS pathway genes. In this context, the findings of the NGS panel were decisive for the diagnosis of JMML. Despite advances in understanding the molecular landscape of JMML, this disease remains challenging, with a wide range of phenotypes and outcomes, ranging from rare forms that resolve spontaneously to aggressive cases with adverse prognosis. Characterization of genomic alterations not only contributes to elucidating the oncogenic mechanisms involved in the pathogenesis of the disease but also provides relevant information for prognosis definition and clinical decision-making.