During the months of November and December 2005, a harmful algal bloom in the northwestern region of Spain caused the accumulation of different algal toxins in several types of shellfish. Many of the shellfish were contaminated at levels above European regulatory limit, presenting serious risks for human health. The analysis of mussels sampled in the affected areas to search for lipophilic toxins, using liquid chromatography tandem mass spectrometry (LC-MS/MS), showed the presence of free okadaic acid (OA) and dinophysistoxin-2 (DTX-2) as well as esters of these toxins. The results also revealed the presence of minor amounts of 13-desmethyl spirolide C (SPX-1) in the analysed samples, although this toxin has never been reported before in Spain. The combination of different MS modes of operation, just as enhanced MS (EMS) and MS(3) experiments, allowed to confirm the first occurrence of spirolides in Spanish shellfish.