This case describes a novel KRAS Q22K mutation with simultaneous KRAS polysomy in a patient with advanced, enteric-type, adenocarcinoma of the lung. Despite the administration of systemic chemotherapy, the disease underwent rapid progression and led to the patient's death in a short period of time. Such an aggressive clinical course suggests that, in this specific case, KRAS dependency was the major genetic driver of poor prognosis. Direct deoxy ribonucleic acid (DNA) sequencing of the KRAS gene allows for the detection of novel KRAS mutations, and it might be advocated in patients with advanced non-small cell lung cancer in view of the emerging role of KRAS as a potential therapeutic target.