In patients with advanced-stage cancer, small biopsies including fine-needle aspirates may be the only opportunity to obtain diagnostic tissue. In the current era of precision medicine, there is an increasing emphasis on the performance of ancillary molecular tests that can provide insights into prognosis and targeted chemotherapeutic options for patient management. Cytopathologists must meet this challenge by accurately diagnosing these fine-needle aspirates and ensuring that adequate material has been obtained for anticipated molecular studies. Herein, we describe a case of a fine-needle aspiration illustrating these principles, especially focusing on the utilization of direct smears for ancillary studies.