Colorectal cancer (CRC) is one of the most common cancer diagnoses in the Western world. It is outnumbered several times by the precursor stage adenoma. The aim of this study was to describe the expression pattern with a double immunohistochemical staining for laminin 5 (γ2) and collagen IV in different colorectal neoplasms. This might be a supplementary tool to morphology in diagnostic dilemmas as microinvasive pT1 tumors and adenomas with pseudoinvasion. Laminin 5 has been shown to stain in invasive tumor cells, while collagen IV highlights the basement membrane (BM). Fifty-seven patients divided according to the primary histopathological diagnoses of tubular adenoma, tubulovillous adenoma, adenoma with pseudoinvasion and glandular adenocarcinoma stages pT1, pT2 or pT3, were included in the study. In normal colonic mucosa, no expression of laminin 5 staining was observed. BM was always intact around normal crypts. In invasive tumors, laminin 5 stained intensely, and the BM was absent or focally discontinuous. The expression in adenomas and in pseudoinvasive areas was less consistent. The study suggests that double immunostaining with collagen IV and laminin 5 might be useful as a supplement for the diagnosis of pT1 CRC. In adenomas, the double staining highlights the areas for the pathologist to pay extra attention. By itself, the double staining cannot determine whether or not there is invasion. Morphology remains the single most important factor in differentiating adenoma and adenoma with pseudoinvasion from early invasive carcinoma.