In the era of smaller and smaller biopsies submitted to pathology departments for diagnosis and the advent of personalized medicine, it has become imperative to efficiently and effectively use patient material to reach individualized, actionable diagnoses. The use of fine needle aspirates and core biopsies as acceptable methods for obtaining sufficient material for hematopoietic neoplasms under nonemergent conditions is debatable. There are, however, scenarios where only limited material is obtainable due to anatomic site, size of the lesion or condition of the patient. In these types of settings, thoughtful approaches and unconventional means are often necessary to reach a diagnosis. In this article, we describe three such scenarios and the unique tactics taken in each to obtain a personalized actionable diagnosis.