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Introduction Diagnostic modalities for thoracic malignancies, especially for lung cancer, have a pivotal impact on further planning. Providing tools should be utilized efficiently to gain a highly positive diagnosis. Thus, we aim to describe the diagnostic approach applied in our population and how each tools frequently used and provide adequate results, so it can be used as the fundamental picture for other centers. Methods A cross-sectional study, involving data from 3661 diagnostic procedures at the Dharmais Cancer Hospital, National Cancer Center in Indonesia, from January 2018-December 2022. Data were from the medical record and analyzed with p Result Brushing with bronchoscopy was the most performed with a positive diagnostic yield of 58.59% cytologically, and VAST were carried out less but obtained the highest positive diagnosis 100% histologically (p = 0.000). Both cytology and histology examination obtained adenocarcinoma as the most common diagnosis (63.80%). Biomolecular EGFR test was the most frequently applied on lung cancer patients (81.43%), besides ALK and PDL-1 (p = 0.000). EGFR and TP53 mutation were highly expressed with next-generation sequencing. Conclusion Multimodality diagnostic procedures should be considered for patients since tissue is an issue, both cytologically and histologically. Biomolecular reflex tests, such as ALK, EGFR, and PD-L1, are essential to apply in lung cancer, and co-mutations can be detected by NGS, such as EGFR-TP53.