Lung cancer is the leading cause of all cancer deaths worldwide with suboptimal prognosis and treatment options. Therefore this study aimed to identify molecular characteristics with a predictive clinical utility which at the same time might represent novel therapeutic targets for human lung adenocarcinoma. Within this study mutations of v-Ki-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS), a gene frequently mutated in lung adenocarcinoma, and their association with enzymatic activities, as assessed by activity-based proteomics, of members of the serine hydrolase (SH) superfamily, a large class of enzymes that have previously been linked to cancer was investigated. The results revealed that the activity of myeloblastin was significantly altered in the lung adenocarcinoma biopsies harboring a KRAS gene mutation. In conclusion myeloblastin is a potential therapeutic target for human lung adenocarcinoma, indicating that the combination of activity-based proteomics with mutational analysis is a valid approach for the discovery of novel biomarkers.