Herein, we compared the effectiveness of longitudinal monitoring for the combination of epidermal growth factor receptor (<i>EGFR)</i> and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (<i>PIK3CA)</i> mutations between saliva-based EFIRM and plasma-based platforms (ddPCR and NGS) in two advanced NSCLC patients undergoing the treatment with osimertinib before and after local ablative therapy (LAT). Here, PIK3CA is linked to non-small cell lung carcinoma.