Background: EGFR mutation is the most common treatable molecular alteration in non-small cell lung cancer (NSCLC), in particular in adenocarcinoma it can be found in 10-15% of our patients (spanish population). But the presence of other commutations in EGFR mutated tumors and its implications has not been well characterized. Methods: We selected patients diagnosed with EGFR mutation non-small cell lung carcinoma (NSCLC) from February 2021 to March 2022 from 4 hospitals in Madrid (most of them from Fundación Jimenez Diaz University Hospital). EGFR status and the presence of commutations was determined by using the AVENIO Tumor Tissue Targeted Kit (a Next Generation Sequencing test). PD-L1 status was determined by immunohistochemistry assay (22C3 pharmDx). Molecular and clinicopathological characteristics were collected and we performed a descriptive analysis of our population. Results: Of the 48 patients evaluated, 68.8% were women and 31.3% were men. 73% were ECOG 0 and 23% ECOG 1 and only 44% were non-smokers, being 18.8% smokers and 37% ex-smokers, most of them with low consumption. The 91.7% were adenocarcinomas and 8.3% were squamous carcinomas. 43.7% were PD-L1 negative and 10.4% were high expressors (PD-L1 > 50%). Of the stage at diagnosis, 60.4% were stage IV and 16.7% were stage III, with 22.9% being stage I and II. Of the Stage IV patients, 87.7% debuted as patients with high disease burden, with only 13.3% being oligometastatic (oligometastatic being understood as those with less than 5 metastases in 3 different organs, including the primary tumor). 40% of them had brain metastasis at the diagnosis. Of the mutational profile, 50% had an exon 19 deletion, 25% had an L858R mutation and the rest had infrequent mutations (12.5% amplification, 10.4% exon 20 insertion and 6.3% exon 18 mutations). In our cases, we evidence that 56.25% of the patients, analyzed by NGS, had another mutation. Of all of them the most frequent was p53 (seen in 55% of the commutated cases), being less frequent others, such as MET and APC amplification (4.2%) and others with a 2.1% (PI3K, BAP1, KRAS, ALKt or HER2 amplification). Finally, we analyzed the progression-free survival (PFS) and overall survival (OS) of commutated patients vs. non-commutated treated with Osimertinib as a first line treatment and, although it was statistically non-significant due to the small sample size (11 vs 9) and the short follow-up, a very positive trend was seen (log-rank test p = 0.055 and p = 0.136 respectively). Conclusions: With the development of NGS, the presence of other commutations besides EGFR have implications that are still unknown, but it appears that it may cause worse OS and PFS. This should be studied in larger cohorts with longer follow-up.