Key Clinical MessageIn the evaluation of patients with longstanding mild thrombocytopenia, emphasis on family history, genetic testing, and collaborative clinical and laboratory‐based family studies can ensure proper diagnosis and monitoring for malignancies.AbstractWe report the diagnostic approach to mild and non‐specific thrombocytopenia with unclear genetic findings in two sisters. Genetic sequencing revealed a rare variant in ETS Variant Transcription Factor 6, which is associated with inherited thrombocytopenia with predisposition to hematologic malignancy. Familial studies provided sufficient evidence for a likely pathogenic classification.