New-onset pancytopenia can be caused by a wide variety of etiologies, leading to a diagnostic dilemma. These etiologies range from congenital bone marrow failure to marrow space-occupying lesions, infection, and peripheral destruction, to name a few. Bone marrow examination, in addition to a detailed clinical history, is often required for an accurate diagnosis. The purpose of this review is to provide a brief overview of many of the causes of new-onset pancytopenia in adults and children, with emphasis on bone marrow findings and recommendations of additional testing and clinical evaluation when needed, with the overall aim of aiding the pathologist's role as a consultant to the patient's treating physician.