e22168 Background: CUP are an heterogeneous family of neoplasms with a dismal prognosis, with empiric chemotherapy as the recommended treatment. The aim of this study was to evaluate the feasibility of a 500-mRNA microarray to identify the tissue of origin in patients with CUP. Methods: Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 22 patients with CUP were prospectively collected. Gene expression profiling was performed using oligonucleotide microarray that contains 495 genes selected as highly differentially expressed between 49 tumor types (CupPrint). Results: The assay was successfully performed on specimens from 18 of the 22 patients (82%). It could not be performed because of a low RNA preservation in the remaining 4 cases. The median age was 57 years (range: 29–70 years). The median delay from tissue shipping to receipt of CupPrint result was 11 days (range: 1–26 days). The most common tissues of origin identified were lung cancer (22%) and colorectal cancer (17%). Of note, a primary cancer which would not be adequately treated by an empiric chemotherapy regimen currently recommended in CUP (like cisplatin-gemcitabine or carboplatin-paclitaxel) was identified in about half patients: kidney cancer (1), hepatocarcinoma (1), colorectal cancer (3), head and neck cancer (2) and cholangiocarcinoma (1). Conclusions: Gene expression profiling of FFPE biopsy specimens from patients with CUP is feasible in a reasonable delay, making it feasible in clinical practice. A phase III randomized trial is planned to compare therapy based on gene expression-suspected primary cancer versus empiric chemotherapy. No significant financial relationships to disclose.