PPI spider implements a robust statistical framework for the interpretation of protein lists in the context of a global PPI network. The input list is translated into a network model according to the topology of the PPI network. Our approach takes into account that the input list may have missing proteins and automatically includes in the network model the most relevant proteins that seem to be missing. As output, our procedure provides a model of protein interactions that represent the most probable scenario of how proteins within the list are connected. Statistical significance of the model is computed by a Monte Carlo simulation procedure.