Our approach to molecular testing of thyroid FNAs combines the detection of selected DNA and RNA mutations utilizing next generation sequencing (NGS) and microRNA expression classification, which independently evaluates the risk of malignancy in these aspirates. An existing platform of DNA mutations and RNA fusions (ThyGenX®) was expanded to include 5 additional oncogene hotspots in RET, ALK, PTEN, GNAS and TERT promoter genes and 32 RNA oncogenic fusions reported in thyroid cancer. The new NGS platform (ThyGeNEXT®) detects DNA mutations in 10 genes and 38 RNA fusions. Here, we describe our one-year clinical experience with the expanded mutation panel and microRNA risk classifier testing of indeterminate thyroid nodules. We also describe estimation of malignancy association for various oncogenic mutations and fusions by incorporating the results of microRNA expression profiling with the NGS results for a large set of clinical specimens.