Pancreatic cancer exhibits a worst prognosis owed to an aggressive tumor progression i.a. driven by chemoresistance or tumor‐stroma‐interactions. The identification of candidate genes, which promote this progression, can lead to new therapeutic targets and might improve patient's outcome. The identification of these candidates in a plethora of genes requires suitable screening protocols. The aim of the present study was to establish a universally usable device which ensures versatile cultivation, screening and handling protocols of cancer cells with the 3D spheroid model, an approved model to study tumor biology. By surface modification and alternative handling of a commercial 384‐well plate, a modified device enabling (i) 3D cultivation either by liquid overlay or by a modified hanging drop method for (ii) screening of substances as well as for tumor‐stroma‐interactions (iii) either with manual or automated handling was established. The here presented preliminary results of cell line dependent dose‐response‐relations and a stromal‐induced spheroid‐formation of the pancreatic cancer cells demonstrate the proof‐of‐principle of the versatile functionality of this device. By adapting the protocols to automation, a higher reproducibility and the ability for high‐throughput analyses were ensured.