STEP 2: Presentation, initial investigations and referral

Early recognition of CUP is important so that specialist assessment and management is not delayed and futile investigations are avoided.

Signs and symptoms: Patients often present to their general or primary medical practitioner with heterogeneous, non-specific symptoms and abnormal test results demonstrating very likely metastatic malignancy but without a clear primary site.

General/primary practitioner investigations:

  • a thorough medical history and physical examination
  • routine blood tests
  • a CT of the chest and abdomen/pelvis
  • a biopsy
  • additional investigations as indicated based on the specific presentation.

Patients with CUP may present with poorly controlled symptoms. Symptomatic care must be provided in parallel with the investigation process.

Referral: Patients with a disease pattern suggesting a specific CUP subset should be referred to a relevant disease-specific oncology team. Patients with non-specific CUP should be referred to an oncologist with adequate experience in managing acute patients with CUP or a general medical oncology service.

The specialist appointment should take place within two weeks of the initial GP referral.


The lead clinician’s (1) responsibilities include:

  • GPs play an important role in coordinating care for patients with CUP, including assisting with side effects and offering support.
  • Provide the patient with information that clearly describes their referral details.

1 Lead clinician – the clinician who is responsible for managing patient care.

The lead clinician may change over time depending on the stage of the care pathway and where care is being provided.