In the present study we show that BCAM negatively regulates the compactness of LAMA5‐rich tumour cell spheroids, and consequently triggers the dispersion of spheroids in a collagen matrix, facilitates the clearance of mesothelial cells at spheroid attachment sites and promotes the trans‐mesothelial invasion of tumour cell spheroids into omental tissue. Here, LAMA5 is linked to neoplasm.