In this study, the simultaneous determination of deoxynivalenol (DON), zearalenone (ZEA), T-2 and HT-2 toxins in foodstuff was investigated. A new kind of multi-mycotoxin immunoaffinity columns (IACs) available on the market (DZT MS-PREP(®)) was tested. A sensitive, selective and accurate method by high-performance liquid chromatography and tandem mass spectrometry was developed, with electrospray ionization mass spectrometer operating in multiple reaction monitoring (MRM) mode, with negative-positive-negative ion switching. The method was used for the analysis of samples marked in Italy, in the frame of official monitoring plans. The advantages of combining IACs and LC-MS/MS technique are as follows: efficient removal of matrix interferences, simple chromatographic outline, high selectivity, low detection limits (DLs) and separation of a wide range of molecules with different physico-chemical properties in a single run. The method was studied on two different matrices, breakfast cereal and baby food, at contamination levels close to Regulation limits (EC) 1126/2007. The recoveries obtained (60-100%) fulfil the performance criteria required by Regulation (EC) 401/2006. The DL is 60 µg/kg for DON and 10 µg/kg for ZEA, T-2 and HT-2. Linearity range of the calibration curves is suitable for adult and baby food.