In the present work, a series of asphaltene solubility fractions extracted from a heavy crude oil have been analyzed using laser desorption ionization (LDI) and atmospheric pressure photoionization (APPI) coupled to Fourier transform ion cyclotron resonance mass spectrometry. The objective is to find how molecular compositional data compare and correlate to information found using other techniques. To accomplish this comparison, a methodology to link the compositional information and the macroscopic behavior is presented and successfully used. In general, we found that average H/C ratios and molecular weights were lower and average densities and average solubility parameters were larger than those determined by other techniques. Values obtained from APPI data were closer than those obtained by LDI data to the reference values. This is indicative that, to estimate bulk properties, APPI might be better suited than LDI. Solubility parameter distributions obtained using APPI data for the classes were shifted to larger values when compared to similar distributions obtained by the solubility profile test. Interestingly, the less soluble the fraction, the closer the APPI distributions were to the solubility profile distributions. All of these results seem to be related to the preferential ionization of the most aromatic molecules in the sample. The preferential detection of high aromaticity molecules suggests that APPI might be particularly suitable to look into the molecular information on the less soluble and, therefore, most troublesome molecules in petroleum. These are the molecules likely to form deposits. Further confirmation of these findings is now underway.