The Idylla Mutation Test System is an automated, PCR-based mutation testing system. The advantages of this system can greatly impact the delivery of precision medicine. We describe our evaluation, validation, and implementation of this system for routine testing of BRAF, EGFR, KRAS, and NRAS using formalin-fixed, paraffin-embedded cancer samples. All four Idylla test systems showed excellent concordance with reference methods. The analytical sensitivity ranged from 94.66% to 100%, depending on the cartridge, and specificity was 100%. A few discordant results were noted and further investigated: KRAS Q61L was misclassified as Q61H; KRAS Q61R was not identified; there was a false-negative EGFR double mutation (L861Q and G719A); and there was a false-negative EGFR double mutation (T790M and exon 19 deletion). The limit of detection was determined to be 1% or 5% for the variants with available reference material. The turnaround time was shortened by 7 days on average. Idylla testing of a cohort of 25 non–small-cell lung cancer samples with insufficient material for next-generation sequencing testing delivered results for all cases and identified actionable results for eight cases. In addition, patient care would have been changed in four of these cases: targeted therapies were identified in two cases, and repeated biopsies would have been avoided in two cases. The Idylla molecular testing system is an accessible, rapid, robust, and reliable testing option for both routine and challenging formalin-fixed, paraffin-embedded specimens.