Cancer cell lines (CCL) are an integral part of modern cancer research but are susceptible to misidentification. The increasing popularity of sequencing technologies motivates the in-silico identification of CCLs based on their mutational fingerprint, but care must be taken when identifying heterogeneous data. We recently developed the proof-of-concept Uniquorn 1 method which could reliably identify heterogeneous sequencing data from selected sequencing technologies. Here we present Uniquorn 2, a generic and robust in-silico identification method for CCLs with DNA/RNA-seq and panel-seq information. We benchmarked Uniquorn 2 by cross-identifying 1612 RNA and 3596 panel-sized NGS profiles derived from 1516 CCLs, five repositories, four technologies and three major cancer panel-designs. Our method achieves an accuracy of 96% for RNA-seq and 95% for mixed DNA-seq and RNA-seq identification. Even for a panel of only 94 cancer-related genes, accuracy remains at 82% but decreases when using smaller panels. Uniquorn 2 is freely available as R-Bioconductor-package 'Uniquorn'.