We demonstrate an early-stage prototype of an image-guided laser ablation system for precise 3D sampling of fresh-frozen tissue samples for subsequent analysis of biomolecules. Utilizing an integrated reflected light microscope and optical coherence tomography, pre-recorded image data (e.g. of characterized tissue slices) can be registered and mapped to the coordinate system for precise aiming and ablation. With this system, we are analyzing a variety of tissue samples from our many collaborators at the University Cancer Center Hamburg (UCCH) for cancer research and demonstrate the system’s feasibility through initial use cases.