With more patients dying from metastasis than from primary cancers, metastasis is a very important area in cancer research. Investigators thereby heavily rely on animal models of metastasis to common organs such as the lung to improve our insight into the pathogenesis and to research novel therapeutic approaches to combat metastasis. In this experimental context, novel tools that allow longitudinal monitoring of lung metastasis in individual animals are highly needed. We have therefore evaluated for the first time microcomputed tomography (μCT) as a very efficient and crossvalidated means to noninvasively and repeatedly monitor metastasis to the lung in individual, free-breathing syngeneic mice. Two individual clones of KLN205 cancer cells were intravenously injected in syngeneic DBA/2 mice and lung metastasis was monitored weekly during 3 weeks using μCT, and was compared with the current gold standard histology and bioluminescence imaging (BLI). μCT enabled us to visualize diffuse tumor morphology and also to extract four different biomarkers that quantify not only tumor load but also aerated space in the lung as a marker of vital lung capacity and potential compensatory mechanisms. Complementary to BLI, applying this novel μCT-based approach enabled us to unravel sensitively and efficiently differences in metastatic potential between two cellular clones. In conclusion, μCT and BLI offer biomarkers that describe different and complementary aspects of lung metastasis, underlining the importance of multimodality follow-up. The added value of μCT findings is important to better assess lung metastasis and host/lung response in preclinical studies, which will be valuable for translational applications.