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Rhabdomyosarcomas with TFCP2fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2break-apart probe (n= 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient’s age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n= 12/14) and soft tissue (n= 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n= 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALKfusion on break-apart FISH (n= 5) nor next-generation sequencing (n= 14). ALKupregulation was frequently associated with an internal deletion at genomic level. TFCP2was fused in 5′ either to EWSR1(n= 6) or FUS(n= 8). EWSR1was involved in both soft tissue cases. FISH with TFCP2break-apart probe was positive in all tested cases (n= 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2Adeletions. FET-TFCP2rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.