Non-Small-Cell Lung Cancer: From Histopathological Classification to Precision Oncology—A Narrative Review

Non-Small-Cell Lung Cancer (NSCLC) represents the most prevalent form of lung cancer and remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease has evolved far beyond traditional histopathological classification. While histology remains foundational, it is no longer sufficient to guide optimal patient management in the era of precision oncology. This review uniquely integrates the full spectrum of NSCLC evaluation, from underlying pathophysiological mechanisms to histological, immunohistochemical, and molecular analyses, culminating in individualized therapeutic planning. We highlight actionable genetic alterations-including EGFR, ALK, ROS1, BRAF, and KRAS-and their roles in guiding targeted therapies, alongside the transformative impact of immune checkpoint inhibitors in selected patients. By emphasizing the interplay between tumor biology, diagnostic workflows, and treatment selection, this review underscores the necessity of comprehensive molecular testing and data integration. Finally, we discuss emerging biomarkers and rational combination strategies that promise to further refine patient stratification and improve outcomes.