Asphaltene molecular weight has been a controversial issue in the past several decades and continues on nowadays. From industrial application point of view, asphaltene molecular weight is important for setting up a heavy oil refining strategy so that the process is efficient and economically viable. If the measured average molecular weight of asphaltene is high and is the true molecular weight, then Substantial amount of energy will be needed, in order to break the molecule into light products during refining process. This is likely not an economical option. On the other, if the measured high molecular weight is due to self-association and the true molecular weight is low (e.g., less than 1500 Da), it will be energetically attractive to refiners to develop heavy oil cracking technology. Vapor pressure osmometry (VPO) has been routinely used for measuring molecular weight. However, it measures the apparent molecular weight and is likely not the true molecular weight. In order to unambiguously measure the molecular weight, it is necessary to develop a convincing technology and a reliable experimental procedure that allows one to measure the molecular weight accurately and consistently. We chose the Atmospheric Pressure Chemical Ionization (APCI) technique and Atmospheric Pressure Photo Ionization (APPI) to measure UG8 asphaltene. Both APCI and APPI have mild ionization processes and have been applied to many unstable drug compounds such as proteins and peptides with reliable outcomes. In addition, we measured the sample on two APPI instruments to compare the results. We also demonstrated how one can choose wrong set of operating parameters and lead to erroneous results. The relevant parameters for APCI and APPI are temperature, voltage, and sample concentration. We chose 0.01 mg/mL as the concentration, much below any known critical aggregation concentration. As for temperature and ionization voltage, we varied systematically varied (T = 300-600degreesC; V = 30-150 V) in order to demonstrate the consistency of the methods and how one can easily make mistake. Through these measurements, an average molecular weight of 400 to 900 Da was obtained for UG8 asphaltene.