INTRODUCTION: The calibrated automated thrombography (CAT) assay is emerging as a reliable tool for real time estimation of thrombin generation (TG) potential. As a time-dependent colorimetric assessment of thrombin quantity generated per sample, it measures the amount of thrombin-cleaved fluorogenic substrate produced, and so is regarded as a better overall indicator of the clotting efficiency and function of the haemostatic process than one stage clotting-time based assays. AIM: We already recognise that the pathways underlying the thrombotic phenotype for different malignancies may be driven by different factors of the coagulation cascade with TG has a common denominator. Two such malignancies with high venous thromboembolism (VTE) incidence are Multiple myeloma (MM) and Pancreatic cancer (PC). Understanding the underlying variations in these two distinct cancer models using patient samples and cell lines might potentially allow individual approaches to identifying thrombotic risk and relevant prevention strategies. MATERIALS AND METHODS: Citrated blood samples were taken from healthy controls, pre-surgical pancreatic cancer and pre-chemotherapy multiple myeloma patients enrolled into ongoing clinical trials. The clotting ability was tested using platelet free plasma (PPP) on a one-step clotting time-based (CT) assay and the TG profiles were evaluated on a Thrombinoscope™ software (Thrombinoscope BV, Maastricht, Netherlands). Solid tumour cells of pancreatic cancer and malignant haematological cell lines were used at various cell concentrations for the CAT assay, which was performed with the addition of platelet-free control plasma or control plasma deficient in coagulation factors VII and XII. RESULTS: At TF concentration conditions of 1 pmol/L, the peak height of thrombin generated on thrombogram curves strongly correlated with CT of patient samples. Compared to healthy controls, pancreatic cancer had higher thrombin peaks (P), shorter lag times (LG), and an overall stronger TG profile than MM. Pancreatic cancer cell lines exhibited higher concentration-dependent TG profiles in control plasma than haematological cell lines, with higher peaks, endogenous thrombin potential (ETP), shorter lag times (LG) and faster times-to-peak (ttPeak). CONCLUSIONS: This study demonstrates that the CAT assay is a useful predictor of the thrombotic phenotype in cancer patients as it gives a more comprehensive overall coagulation profile than one stage CT-based assays. It shows that for patient samples and cell lines, the similarities and differences that exists in the TG potential, significantly depends on specific coagulation factors present in the intrinsic or extrinsic arms of the clotting cascade.