Background: Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of cell-free circulating free nucleic acid (DNA and RNA) due to its high sensitivity, low cost, and fast reading, since it dispenses bioinformatics, making it an appropriate alternative to new generation sequencing (NGS) for the detection of biomarkers to guide molecularly targeted cancer therapy. The assay covers main actionable hotspot alterations across many actionable genes: EGFR(mutations), ALK (fusion, mutations), ROS1(fusion), BRAF(mutations), KRAS (mutations), NRAS(mutations), PIK3CA (mutations), ERBB2(CNV- copy number variation), ESR1(mutations), KIT(CNV) and PDGFRA(CNV). Therefore, our genes can be used in panels, both in therapeutically applied genotyping and in detecting molecular responses as well as in secondary resistance to tumors such as NSCLC, breast, cervix. rectal, GIST, melanoma and pancreas. Methods: dd-PCR was performed using the QX200 system (BIO-RAD, Hercules). The extraction of DNA and RNA was done using the magnetic beads technique of Thermofisher's MagMAX Kit. All samples were tested in duplicate. Up to now, 108 metastatic cancer patients were tested: NSCLC - 28 (26%), breast - 22 (20%), colorectal - 22(20%), melanoma - 18(17%), pancreas - 8(7%), ovarian - 6(6%), salivary glands - 2 (4%) and GIST 2(4%). Results: Significant genomic alterations were detected in 38(35%) patients: 10 (9%) mutations in the KRAS G12V gene (all in colorectal cancer), 10 (9%) ERBB2 amplification (breast cancer), 4 (3.65%) EGFR L858R mutations (NSCLC), 4 (3.5%) EGFR del19 mutations (NSLC), 4 (3.5%) EGFR T790M mutations (NSCLC), 4 (3.5%) BRAF-V600E mutations (colon and melanoma), 2 (1.8%) ALK-EML4 fusion (NSCLC). The MAF (Mutant Allele Fraction) ranged from 0.9% to 24%. In all cases, the results were decisive for the indication or change of a targeted therapy. Median turnaround time was 36 hours and the average cost of the panels was around 500 USD (median of 4 genes per panel). Conclusions: Our results suggest that dd-PCR is a highly sensitive method and could be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors.