A diagnosis of Carcinoma of Unknown Primary (CUP) is made when a patient presents with metastatic disease for which no primary cancer can be identified despite extensive clinical assessment, imaging, and pathological evaluation. CUP is said to account for about 3-5% of cancer cases and is decreasing in incidence with better diagnostic work-up of patients but is generally associated with a high mortality. CUP can be further classified into clinicopathological subsets with 10-15% of cases being in a favourable risk subset. Diagnostic and work-up guidelines have been suggested by international groups, with recent NICE guidelines recommending patient care is performed by dedicated CUP multi-disciplinary teams. In February 2012 PeterMac established a CUP specific clinic. Referrals of patients with imaging suggesting a possible diagnosis of CUP, with or without a biopsy, are seen rapidly and assessed as per recommendations. PET/CT is used to target the optimal area for biopsy and look for evidence of a primary. Where possible, patients are enrolled in the Cancer 2015 project which involves molecular profiling of tumours and collection of quality of life data. In addition, biopsy tissue is sent for the CUPGUIDETM site of origin test. Patients determined to have a specific cancer diagnosis are subsequently referred to the relevant service for specialized management eg. uro-oncology. CUP patients continue to be managed by the clinic with local or systemic treatment as well as consideration of trial therapies if appropriate. The initial experience and challenges will be described. It is hoped that the clinic will continue to develop to become a rapid comprehensive assessment service which will allow prompt treatment and supportive care recommendations, as well as being a focus for future research into this neglected cancer.