An adequate reproducibility in the description of tissue architecture is still a challenge to diagnostic pathology, sometimes with unfortunate prognostic implications. To assess a possible diagnostic and prognostic value of quantitiative tissue architecture analysis, structural features based on the Voronoi Diagram (VD) and its subgraphs were developed and tested.A series of 27 structural features were developed and tested in a pilot study of 30 cases of prostate cancer, 10 cases of cervical carcinomas, 8 cases of tongue cancer and 8 cases of normal oral mucosa. Grey level images were acquired from hematoxyline‐eosine (HE) stained sections by a charge coupled device (CCD) camera mounted on a microscope connected to a personal computer (PC) with an image array processor. From the grey level images obtained, cell nuclei were automatically segmented and the geometrical centres of cell nuclei were computed. The resulting 2‐dimensional (2D) swarm of pointlike seeds distributed in a flat plane was the basis for construction of the VD and its subgraphs. From the polygons, triangulations and arborizations thus obtained, 27 structural features were computed as numerical values. Comparison of groups (normal vs. cancerous oral mucosa, cervical and prostate carcinomas with good and poor prognosis) with regard to distribution in the values of the structural features was performed with Student's t‐test.We demonstrate that some of the structural features developed are able to distinguish structurally between normal and cancerous oral mucosa (P=0.001), and between good and poor outcome groups in prostatic (P=0.001) and cervical carcinomas (P=0.001).We present results confirming previous findings that graph theory based algorithms are useful tools for describing tis‐ sue architecture (e.g., normal versus malignant). The present study also indicates that these methods have a potential for prognostication in malignant epithelial lesions.