Combined small-cell lung carcinoma is a rare and heterogeneous lung cancer characterized by the coexistence of small-cell and non-small-cell components. Concurrent epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement in combined small-cell lung carcinoma is extremely uncommon and presents diagnostic and therapeutic challenges. We report a 63-year-old man presenting with cough and right-sided chest pain. Imaging revealed a right lower lobe mass with mediastinal lymphadenopathy. Initial biopsy showed adenocarcinoma without actionable mutations. Following a limited response to neoadjuvant chemotherapy, right lower lobectomy was performed. Histopathological examination revealed combined small-cell carcinoma and adenocarcinoma, while molecular analysis identified concurrent epidermal growth factor receptor exon 19 deletion and anaplastic lymphoma kinase rearrangement. Lymph nodes were negative for metastasis. Postoperative targeted therapy was initiated, and follow-up imaging showed no evidence of recurrence. This case highlights tumour heterogeneity and the importance of comprehensive pathological and molecular evaluation in guiding personalized therapy. © The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).