We performed a comparison of electrospray droplet impact (EDI) with laser desorption ionization (LDI) and matrix-assisted laser desorption/ionization (MALDI) to analyze several organic pigments, including Pigment Yellow 93, Pigment Yellow 180, and Pigment Green 36, as test samples. These samples are poorly soluble in standard solvents. In EDI, samples were prepared by direct deposition of the powder samples on the substrates. No matrices were used. We also found that EDI was an easy, versatile method for testing as-received samples. However, some fragment ions were generated in the EDI process. In contrast, in negative-mode MALDI mass spectrometry using tetrathiafulvalene (TTF) as a matrix, we found that fragment ions were much less abundant than in positive-mode MALDI, EDI, or LDI. Using TTF as a matrix, the most abundant analyte ions produced were radicals or deprotonated anions.