Pathological lesions in the oral cavity could be the initial signs of underlying systemic disorders such as hematopoietic diseases. The presence of dental plaque and calculus could be as local predisposing factors that may exacerbate the oral lesion. This current report presents a case of a 16-year-old boy with acute necrotizing gingivitis as a manifestation of myelodysplastic syndrome/myeloproliferative neoplasms. The lesion was painful, tends to reappear at different periodontal regions when the patient in the immune-compromised state which resulted in difficulty in eating and tooth brushing. The lesion was under-controlled after non-surgical periodontal therapy was advocated followed by close monitoring of oral hygiene care. The physician and dentist must be aware of the changes in the oral health status of patients suffering from these hematological disorders as optimum oral hygiene maintenance is deemed important to avoid the debilitating condition.