Metastatic melanoma is a cancer for which vascularization is not a diagnostic criterion. The aim of this study was to evaluate the applicabilities of laser speckle contrast imaging (LSCI) and contrast enhanced ultrasound (CEUS) in a mouse-model. B16F10 cells were xenografted to C57BL/6 mice. Mice were treated with anti-PD1 or 0.9% NaCl and tumor volume was measured daily. CEUS and LSCI were performed weekly. No difference in tumor growth or median survival were observed between treated and no-treaated mice. No significant difference in tumor volume measurement comparing caliper and CEUS was observed. LSCI and CEUS analyses showed a decrease in tumor perfusion in both groups of mice. Although both CEUS and LSCI are useful for measuring tumor volume, LSCI appears to be more robust and effective for monitoring tumor microcirculation. Non-invasive investigations are needed to better predict tumor vascularization: CEUS and LSCI have a good applicability in a mice model.