There are at least two important factors that lead to major misunderstandings when people of different cultures are communicating with one another.
The first of these factors is differences in verbal language. People from different cultures often speak different languages as their native tongues. Therefore, when they speak, at least one of them is speaking in a language that is not their own. At the very least, they speak the same basic language, but with cultural variations. This means that people from different cultures might have different understandings of the same words and phrases. This can cause serious misunderstandings.
The second factor is in nonverbal communication. Different cultures ascribe different meanings to things like gestures and body language. A classic example of this is the meaning ascribed to eye contact. In Western cultures such as that of the United States, people tend to expect eye contact and to believe that it shows sincerity. In many other cultures, making eye contact with someone else can be very disrespectful. This sort of difference can also be an important source of misunderstanding when people of different cultures communicate with one another.